The long term objective of this project is to define clinically important factors associated with increased risk for the development of destructive periodontal disease. Identification of these factors and understanding their mechanism of action will lead to intervention studies in which the risk factor is altered as a strategy to prevent periodontal destruction and loss of teeth. Specifically, we propose a longitudinal study of a large cohort to determine if previously identified risk indicators such as diabetes mellitus, smoking, specific periodontal pathogens and stress/distress, and coping behaviors are associated with an increased incidence of periodontitis. Changes in periodontal status (incidence) will be based on changes in attachment levels accurately measured with an automated periodontal probe, and on changers in alveolar crestal heights measured by computer- assisted analysis of radiographs. Psychosocial factors are assessed using a battery of seven instruments which measure life events, chronic stress, distress, hassles and uplifts, coping; as well as explanatory style, and control over events in daily life. Next, we propose to study periodontitis patients who have diabetes mellitus or who smoke, to determine to what extent these putative risk factors affect the rate of periodontal destruction. This will be accomplished in longitudinal case control studies where the putative risk factors are isolated and controls are matched for age and pathogenic bacteria, and in the case of the diabetics also matched for smoking. The rate of periodontal destruction and incidence of new disease will be assessed by standardized automated periodontal probing and by changes in alveolar crestal heights from computer-assisted analysis of radiographs. A battery of eight subgingival target organisms will be quantitated by specific antibody-based techniques adapted to use for large numbers of samples as generated in these longitudinal samples. Humoral immunity will also be measured. Finally, we propose to evaluate the mode of oral colonization with periodontal pathogens by assessing the clonal distribution of organisms in households and families affected by periodontitis. Colonization studies will be carried out using molecular genetic techniques such as restriction enzyme analysis, and the randomly primed polymerase chain reaction. These studies will assess the distribution of organisms in family members where at least one member has severe periodontitis, and several are infected by the target organisms A. actinomycetemcomitans, P. gingivalis, or B. forsythus. Identification of; important risk factors, either causative or predictive, will facilitate efforts to develop and implement preventive measures designed to reduce tooth loss and edentulousness resulting from destructive periodontal disease. These measures then can be targeted to high risk populations and minorities in concert with the oral health objectives of "Healthy People: 2000."